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Background: Sleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 ( MECP2 ) gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients., Methods: A total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7-35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L'Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients' contributions to the surrounding water vapor partial pressure [P H2O (pt)] and carbon dioxide [P CO2 (pt)] were indirectly estimated., Results: Of the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03-82%)] and HR/LF [median: 3.75 (interquartile range 3.19-5.05)] were elevated, independent from the wake-sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients ( p  ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing., Conclusion: Our findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression., Competing Interests: The co-author AmB is an advisor of Accyourate Group SpA, a sponsor of the research. PM was employed by Croce Rossa Italiana. AlB was employed by Italian Color Solutions I.C.S. S.r.l. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Leoncini, Boasiako, Di Lucia, Beker, Scandurra, Vignoli, Canevini, Prato, Nobili, Nicotera, Di Rosa, Chiarini, Cutrera, Grosso, Lazzeri, Tongiorgi, Morano, Botteghi, Barducci and De Felice.)

KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: -0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The association between autism spectrum disorders (ASD) and epilepsy has been extensively documented, and the estimated prevalence varies depending upon the selected population and the clinical characteristics. Currently, there are a lack of studies assessing the patient care pathways in ASD, particularly for comorbidity with epilepsy, despite its personal, familial, and economic impacts. Genetic abnormalities are likely implicated in the association of ASD and epilepsy, although they are currently detectable in only a small percentage of patients, and some known genetic and medical conditions are associated with ASD and epilepsy. There is no specificity of seizure type to be expected in children and adolescents with ASD compared with other neurodevelopmental disorders or epileptic syndromes. Treatment options include antiepileptic drugs (AED) and developmentally-based early interventions for ASD. Carbamazepine and lamotrigine are the most used AED, but further studies are needed to more precisely define the most suitable medications for this specific group of children with ASD.

Genetic defects in the SHANK2 gene, encoding for synaptic scaffolding protein, are associated with a variety of neurodevelopmental conditions, including autism spectrum disorders and mild to moderate intellectual disability. Until now, limited patient clinical descriptions have been published. Only 13 unrelated patients with SHANK2 pathogenic variations or microdeletions have been reported worldwide. By Exome Sequencing, we identified a de novo stop-gain variant, c.334C>T, p.(Gln112*), in an Italian patient with a neurodevelopmental disorder. The patient (9 years old) presented the following facial features: a flat profile, thick eyebrows, long eyelashes, a bulbous nasal tip and a prominent columella, retracted ears, dental anomalies. The patient showed speech delay and mild neuromotor delay but not autism spectrum disorder. In conclusion, this patient with a novel pathogenic variant in SHANK2 enlarges the phenotypic spectrum of SHANK2-mutated patients and demonstrates that the severity of SHANK2-associated disorders is highly variable.

Background: Breathing abnormalities are common in Rett syndrome (RTT), a pervasive neurodevelopmental disorder almost exclusively affecting females. RTT is linked to mutations in the methyl-CpG-binding protein 2 ( MeCP2 ) gene. Our aim was to assess the clinical relevance of apneas during sleep-wakefulness cycle in a population with RTT and the possible impact of apneas on circulating oxidative stress markers., Methods: Female patients with a clinical diagnosis of typical RTT ( n = 66), MECP2 gene mutation, and apneas were enrolled (mean age: 12.5 years). Baseline clinical severity, arterial blood gas analysis, and red blood cell count were assessed. Breathing was monitored during the wakefulness and sleep states (average recording time: 13 ± 0.5 h) with a portable polygraphic screening device. According to prevalence of breath holdings, the population was categorized into the wakefulness apnea (WA) and sleep apnea (SA) groups, and apnea-hypopnea index (AHI) was calculated. The impact of respiratory events on oxidative stress was assessed by plasma and intra-erythrocyte non-protein-bound iron (P-NPBI and IE-NPBI, respectively), and plasma F 2 -isoprostane (F 2 -IsoP) assays., Results: Significant prevalence of obstructive apneas with values of AHI > 15 was present in 69.7% of the population with RTT. The group with SA showed significantly increased AHI values > 15 ( p = 0.0032), total breath holding episodes ( p = 0.007), and average SpO 2 ( p = 0.0001) as well as lower nadir SpO 2 ( p = 0.0004) compared with the patients with WAs. The subgroups of patients with WA and SA showed no significant differences in arterial blood gas analysis variables ( p > 0.089). Decreased mean cell hemoglobin (MCH) ( p = 0.038) was observed in the group with WAs. P-NPBI levels were significantly higher in the group with WA than in that with SAs ( p = 0.0001). Stepwise multiple linear regression models showed WA being related to nadir SpO 2 , average SpO 2 , and P-NPBI (adjusted R 2 = 0.613, multiple correlation coefficient = 0.795 p < 0.0001), and P-NPBI being related to average SpO 2 , blood PaCO 2 , red blood cell mean corpuscular volume (MCV), age, and topiramate treatment (adjusted R 2 = 0.551, multiple correlation coefficient = 0.765, p < 0.0001)., Conclusion: Our findings indicate that the impact of apneas in RTT is uneven according to the sleep-wakefulness cycle, and that plasma redox active iron represents a potential novel therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Leoncini, Signorini, Boasiako, Scandurra, Hayek, Ciccoli, Rossi, Canitano and De Felice.)

Introduction : Autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD) are the two most common neurodevelopmental disorders observed in childhood. The DSM-5 accepts a combined diagnosis of ADHD and ASD, while the DSM-IV did not. The aim of this study was to identify and evaluate the adaptive profile of children and adolescents with a diagnosis of comorbid ADHD and ASD, in comparison with adaptive functioning in subjects with a diagnosis of only ASD or ADHD. Materials and Methods: Ninety-one children (77 boys, 14 girls), aging from 3.1 to 13.4 years (mean age: 8.3 ± 7.2), who met the criteria for a diagnosis of ASD and/or ADHD were enrolled. A neuropsychological evaluation involving cognitive and adaptive assessment was conducted using the Autism Diagnostic Observation Schedule - Second Edition (ADOS-2), the Conners' Parent Rating Scale - Revised: Long Version (CPRS-R), the Wechsler Intelligence Scale - Fourth Edition or the Griffiths Mental Developmental Scales - Extended Revised, the Vineland Adaptive Behaviour Scale - Second Edition (VABS-II). Conclusion: As to the adaptive skills in the three groups evaluated, a worse general profile was ascertained in the ASD and in ASD plus ADHD groups in comparison with respect to the ADHD-only group. With VABS-II evaluation, we found significant differences among the three groups across all domains and combined scores: Communication (F = 18.960; p < 0.001), Socialization (F = 25.410; p < 0.001), Daily Living Skills (F = 19.760; p < 0.001), Motor (F = 9.615; p < 0.001), and Adaptive behavior composite [ABC] (F = 29.370; p < 0.001). Implications of neurodevelopmental double diagnosis such as ASD plus ADHD are discussed.

A historical review of the concepts of self-consciousness is presented, highlighting the important role of the body (particularly, body perception but also body action), and the social other in the construction of self-consciousness. More precisely, body perception, especially intermodal sensory perception including kinesthetic perception, is involved in the construction of a sense of self allowing self-other differentiation. Furthermore, the social other , through very early social and emotional interactions, provides meaning to the infant's perception and contributes to the development of his/her symbolization capacities. This is a necessary condition for body image representation and awareness of a permanent self in a time-space continuum (invariant over time and space). Self-image recognition impairments in the mirror are also discussed regarding a comprehensive developmental theory of self-consciousness. Then, a neuropsychological and neurophysiological approach to self-consciousness reviews the role of complex brain activation/integration pathways and the mirror neuron system in self-consciousness. Finally, this article offers new perspectives on self-consciousness evaluation using a double mirror paradigm to study self- and other- image and body recognition.

22q11.2 Deletion Syndrome (22q11 DS) is a multisystemic condition that may also include neuropsychiatric disorders. We present a case of a 15-year-old boy that was evaluated for social difficulties, and anxiety with the above genetic abnormality. Clinical features were rather complex as different neuropsychiatric symptoms emerged from assessment and clinical evaluation. As a result we propose that Multiple Complex Developmental Disorder (MCDD) would be the best fitting comprehensive diagnosis to be added to the DSM-IV category of Pervasive Developmental Disorder-Not Otherwise Specified.

Several cases of interstitial deletion encompassing band 18q12.3 are described in patients with mild dysmorphic features, mental retardation and impairment of expressive language. The critical deleted region contains SETBP1 gene (SET binding protein 1). Missense heterozygous mutations in this gene cause Schinzel-Giedion syndrome (SGS, MIM#269150), characterized by profound mental retardation and multiple congenital malformations. Recently, a 18q12.3 microdeletion causing SETBP1 haploinsufficiency has been described in two patients that show expressive speech impairment, moderate developmental delay and peculiar facial features. The phenotype of individual with partial chromosome 18q deletions does not resemble SGS. The deletion defines a critical region in which SETBP1 is the major candidate gene for expressive speech defect. We describe an additional patient with the smallest 18q12.3 microdeletion never reported that causes the disruption of SETBP1. The patient shows mild mental retardation and expressive speech impairment with striking discrepancy between expressive and receptive language skills. He is able to communicate using gestures and mimic expression of face and body with surprising efficacy. The significant phenotypic overlap between this patient and the cases previously reported enforce the hypothesis that SETBP1 haploinsufficiency may have a role in expressive language development., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

This is a review of the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autistic spectrum disorders (ASD). The main clinical characteristics are impairment in social skills, communication difficulties, repetitive movements and behaviors, including stereotypies. Pharmacotherapy is mainly directed at the so-called target symptoms, ie, behavioral disorders and the various kinds of repetitions associated with ASD. According to the available data, risperidone seems to be moderately efficacious and safe for treating behavioral disorders. 4 double blind controlled trial. 3 reanalysis studies, and 12 open studies have documented the role of risperidone in children with ASD. Controlled studies have been thoroughly considered in this review.